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Relationship of insulin dose, A1c lowering, and weight in type 2 diabetes: comparing insulin glargine and insulin detemir.

ABSTRACT:

Background

A pooled analysis of randomized controlled trials of individuals with type 2 diabetes mellitus (T2DM) was conducted to compare dosing and impact of two basal insulin analogs, insulin glargine (glargine) and insulin detemir (detemir), on weight and hemoglobin A1c (A1c).

Methods

Twenty-two studies of at least 20 weeks in duration in individuals with T2DM initiating glargine/detemir were included. Results were combined using a weighted-average method and a bivariate random effect model. Outcomes included changes in weight, A1c, and insulin dose from study start to end.

Results

One study was head-to-head comparison of glargine and detemir. Detemir (four studies) was administered once or twice daily, with 50% starting on detemir once daily but needing therapy intensification. Glargine was used once daily in all 22 studies. The Egger test was borderline significant for change in weight over the course of the treatment for glargine (0.29; 90% confidence interval [CI] -0.01, 0.58), and heterogeneity was not observed for detemir (-0.18; 90% CI -0.59, 0.23). Heterogeneity was observed for change in A1c over the course of the treatment (glargine, -1.19, 90% CI -1.74, -0.63; detemir, -2.65, 90% CI -4.86, -0.45). Nonheterogeneity for change in A1c over the course of the treatment was achieved by excluding five studies for glargine and one study for detemir; however, all studies were included in subsequent analyses. In the unadjusted model, glargine and detemir showed similar results for mean A1c change (-1.4% vs. -1.4%), weight gain (2.5 vs. 1.7 kg), and weight/A1c (1.8 vs. 1.2 kg/%). A significantly higher detemir dose was needed to achieve the same A1c change (51.5 vs. 38.8 U/day).

Conclusions

Although absolute weight gain was higher with glargine versus detemir, weight gain per A1c change was similar. A higher detemir dose was required to achieve a similar A1c reduction.

SUBMITTER: Dailey G

PROVIDER: S-EPMC3000926 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.ObjectivesTo assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.Search strategyWe searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.Selection criteriaAll randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.Data collection and analysisTwo authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.Main resultsThis review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.Authors' conclusionsOur analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

Project description:Aims/hypothesisThis 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients.MethodsInsulin-naive adults (n=582, HbA(1c) 7.5-10.0%, BMI <or= 40.0 kg/m(2)) were randomised 1:1 to receive insulin detemir or glargine once daily (evening) actively titrated to target fasting plasma glucose (FPG) <or= 6.0 mmol/l. An additional morning insulin detemir dose was permitted if pre-dinner plasma glucose (PG) was >7.0 mmol/l after achieving FPG <7.0 mmol/l. Due to labelling restrictions, no second glargine dose was allowed.ResultsBaseline HbA(1c) decreased from 8.6 to 7.2 and 7.1% (NS) with detemir and glargine, respectively. FPG improved from 10.8 to 7.1 and 7.0 mmol/l (NS), respectively. With detemir, 45% of participants completed the study on once daily dosing and 55% on twice daily dosing, with no difference in HbA(1c). Overall, 52% of participants achieved HbA(1c) <or= 7.0%: 33% (detemir) and 35% (glargine) without hypoglycaemia. Within-participant variability for self-monitored FPG and pre-dinner PG did not differ by insulin treatment, nor did the relative risk of overall or nocturnal hypoglycaemia. Modest reductions in weight gain were seen with detemir vs glargine in completers (3.0 vs 3.9 kg, p=0.01) and in the intention-to-treat population (2.7 vs 3.5 kg, p=0.03), primarily related to completers on once-daily detemir. Mean daily detemir dose was higher (0.78 U/kg [0.52 with once daily dosing, 1.00 U/kg with twice daily dosing]) than glargine (0.44 IU/kg). Injection site reactions were more frequent with detemir (4.5 vs 1.4%).Conclusions/interpretationSupplementation of oral agents with detemir or glargine achieves clinically important improvements in glycaemic control with low risk of hypoglycaemia. Non-inferiority was demonstrated for detemir using higher insulin doses (mainly patients on twice daily dosing); weight gain was somewhat reduced with once daily insulin detemir.

Project description:AimsA variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.MethodsA systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.ResultsTwenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).ConclusionFor the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.

Project description:IntroductionUncontrolled type 2 diabetes (T2D) is associated with an increased risk of micro- and macrovascular complications and mortality. The impact of basal insulins on the risks of mortality and cardiovascular mortality in people with T2D has not been thoroughly investigated in real-world settings. The aim of the present real-word study was to investigate differences in mortality among insulin-naïve people with T2D who initiated insulin detemir (detemir) and insulin glargine (glargine).MethodsWe assessed all-cause and cardiovascular mortality in people with T2D, aged ≥ 40 years and insulin-naïve at treatment initiation. People were identified from the United Kingdom Clinical Practice Research Datalink GOLD national database (2004-2019). Database information included prescribed medications, demographic and clinical variables and mortality. Cause of death was obtained from the Office for National Statistics (ONS). For mortality, 24 clinically relevant confounders were considered and adjusted for using Cox regression analyses.ResultsThe total cohort included 12,847 people with T2D, including 3031 who commenced detemir and 9816 who commenced glargine. Median age was 66.8 years and median diabetes duration was 7.6 years. From the total cohort, 3231 deaths occurred during follow-up and 6897 people were eligible for linkage to the ONS for cardiovascular mortality data (528 cardiovascular deaths). The adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.86 (0.79; 0.95) for all-cause mortality and 0.83 (0.67; 1.03) for cardiovascular mortality, in favour of detemir versus glargine. These associations were more pronounced among people with obesity (body mass index ≥ 30 kg/m2), with HRs (95% CI) of 0.79 (0.69; 0.91) and 0.69 (0.50; 0.96) for all-cause and cardiovascular mortality, respectively.ConclusionIn this real-world observational study, there was an association between all-cause mortality and basal insulin choice in insulin-naïve people with T2D; the mortality risk was lower with detemir versus glargine after adjustment for potential confounders.